Self-medication among children and adolescents.
Self-medication includes several forms through which the individual him/herself or the ones responsible for him/her decide, without medical evaluation, which drug they will use and in which way for the symptomatic relief and "cure" of a condition. It involves sharing drugs with other members of the family and social group, using leftovers from previous prescriptions or disrespecting the medical prescription either by prolonging or interrupting the dosage and the administration period prescribed. Although few researches have studied aspects of self-medication in children and adolescents, some authors have reported a high prevalence of self-medication in this age group. Similar to adults, the highest consumption of drugs involves the use of analgesics, antipyretics and anti-inflammatory drugs followed by antibiotics. This review describes the global pattern of self-medication in children and adolescents, and discusses public policies aiming to promote health interventions and strategies to prevent self-medication.


Patients' knowledge and awareness of safe handling of oral anticancer agents at Sultan Qaboos University Hospital in Oman.
Safe handling of oral anticancer agents is of great concern. There is a lack of clear, national guidelines on how patients can safely handle and dispose of unwanted medications. We aimed to evaluate the safe handling, storage, and disposal of oral anticancer drugs among cancer patients and caregivers at home. This cross-sectional survey of adult cancer patients (or their adult caregivers) used a closed-ended questionnaire from May 2019 to March 2020. A total of 257 patients (50 ± 15 years; range: 18-93 years) were enrolled; however, only 91% (233/257) reported self-administering oral anticancer medications. Caregivers were more likely to administer oral anticancer agents for patients ≥60 years than those <40 years old (63% vs. 8%; P = 0.001). Most patients (52%; 133/257) did not wash their hands after administering the drug; 74% (164/222) of the respondents reported that their medications were kept in a bedroom cabinet, while 18% (40/222) stored their medications in a refrigerator, and 5% (12/222) in a kitchen cabinet. A total of 55% (68/124) of patients returned their excess oral chemotherapy medications to the hospitals; however, 36% (45/124) disposed of their unused oral chemotherapy drugs in a household garbage container. While two-thirds of patients stored their oral anticancer medications properly, more than half used inappropriate handling procedures. Disposal practices were inconsistent and did not adhere to the reported international guidelines.


The overlap between cyberbullying and traditional bullying.
Cyberbullying appears to be on the rise among adolescents due in part to increased access to electronic devices and less online supervision. Less is known about how cyberbullying differs from traditional bullying which occurs in person and the extent to which these two forms overlap. Our first aim was to examine the overlap of traditional bullying (relational, verbal, and physical) with cyberbullying. The second aim examined student- and school-level correlates of cyber victimization as compared to traditional victims. The final aim explored details of the cyberbullying experience (e.g., who sent the message, how was the message sent, and what was the message about). Data came from 28,104 adolescents (grades, 9-12) attending 58 high schools. Approximately 23% of the youth reported being victims of any form of bullying (cyber, relational, physical, and verbal) within the last month, with 25.6% of those victims reporting being cyberbullied. The largest proportion (50.3%) of victims reported they were victimized by all four forms, whereas only 4.6% reported being only cyberbullied. Multilevel analyses indicated that as compared to those who were only traditionally bullied, those who were cyberbullied were more likely to have externalizing (odds ratio = 1.44) and internalizing symptoms (odds ratio = 1.25). Additional analyses examined detailed characteristics of the cyberbullying experiences, indicating a relatively high level of overlap between cyber and traditional bullying. Implications for preventive interventions targeting youth involved with cyberbullying and its overlap with other forms of bullying are discussed.


Single-crystal elastic properties of the modified spinel (Beta) phase of magnesium orthosilicate.
The single-crystal elastic moduli of the modified spinel structure (beta phase) of magnesium orthosilicate (Mg(2)SiO(4)) have been measured by Brillouin spectroscopy under ambient conditions. Single crystals with dimensions up to 500 micrometers were grown at 22 gigapascals and 2000 degrees C over a period of 1 hour. Growth of crystals larger than 100 micrometers was achieved only when the pressure was within 5 percent of the pressure of the phase boundary separating the beta- and gamma-phase stability fields. A comparison of the elastic properties of the modified spinel phase with those of the olivine phase suggests that the 400-kilometer seismic discontinuity in the earth's mantle can be described by a mantle with 40 percent olivine. These results confirm that the 400-kilometer discontinuity can be due to the transition from olivine to modified spinel. The amount of olivine that must be present is less than that in a pyrolite model, although the results do not exclude pyrolite as a possible mantle model.


Quality improvement in the era of health reform.
More and more scrutiny is certain for the health care field. The intense interest in medical quality management that has been a factor in the field for many years is certain to increase under any reform that the system undergoes. This is a unique opportunity for physician executives to play a leading role in the future course of health care delivery. The alternative of their involvement will be almost total control of the issue by regulators.


Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice.
Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the effect of these nanoparticles on genomic DNA integrity and inflammation induction in the gastric tissues. Hence, this study estimated the effect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and inflammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to significant elevations in DNA damage induction and ROS generation, in contrast to the non-significant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and inflammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH)2 nanoparticles.


Prevalence and influencing factors of PTSD symptoms among healthcare workers: A multicenter cross-sectional study during the surge period of the COVID-19 pandemic since December 2022 in the Chinese mainland.
China has experienced a surge period of COVID-19 pandemic since December 2022. Healthcare workers (HCWs) were exposed to huge workload under high risk of being infected, and significant levels of trauma, which might cause Post-traumatic Stress Disorders (PTSD) symptoms in HCWs. To identify the prevalence of PTSD symptoms among HCWs in the Chinese mainland during the surge period of the COVID-19 pandemic; to explore their psycho-social factors of PTSD symptoms. A multicenter cross-sectional study was conducted among HCWs in Chinese mainland from January 5 to February 9, 2023, covering seven geographical regions. 6552 participants were recruited by convenience sampling. Data were collected on demographic characteristics, work-related factors, and psychological factors by online questionnaires. Univariate analysis and binary logistic regression were used to determine the influencing factors of PTSD symptoms. The prevalence of PTSD symptoms among HCWs was 37.49 %. A higher level of mindfulness, resilience, and perceived social support were protective factors. Female gender, nurses, higher educational attainment, married status, more working years, higher perceived risk of contracting COVID-19 due to work, and higher perceived work intensity were risk factors. High prevalence of PTSD symptoms among HCWs necessitates psychological interventions. Tailored interventions, designed by professional psychiatrists, should be tailored to address the stressors. A comprehensive approach, incorporating mindfulness, resilience-building, and perceived social support enhancement, is vital to bolster the mental well-being of HCWs exposed to traumatic events, thus mitigating the impact of PTSD effectively. Additionally, it is essential to provide support to HCWs with other potential risk factors.


Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.
Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels.


The comet-tail artifact. An ultrasound sign of alveolar-interstitial syndrome.
Can ultrasound be of any help in the diagnosis of alveolar-interstitial syndrome? In a prospective study, we examined 250 consecutive patients in a medical intensive care unit: 121 patients with radiologic alveolar-interstitial syndrome (disseminated to the whole lung, n = 92; localized, n = 29) and 129 patients without radiologic evidence of alveolar-interstitial syndrome. The antero-lateral chest wall was examined using ultrasound. The ultrasonic feature of multiple comet-tail artifacts fanning out from the lung surface was investigated. This pattern was present all over the lung surface in 86 of 92 patients with diffuse alveolar-interstitial syndrome (sensitivity of 93.4%). It was absent or confined to the last lateral intercostal space in 120 of 129 patients with normal chest X-ray (specificity of 93.0%). Tomodensitometric correlations showed that the thickened sub-pleural interlobular septa, as well as ground-glass areas, two lesions present in acute pulmonary edema, were associated with the presence of the comet-tail artifact. In conclusion, presence of the comet-tail artifact allowed diagnosis of alveolar-interstitial syndrome.


Candidate salivary biomarkers associated with alveolar bone loss: cross-sectional and in vitro studies.
This cross-sectional study evaluated the association between radiographic evidence of alveolar bone loss and the concentration of host-derived bone resorptive factors (interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6, prostaglandin-E2), and markers of bone turnover [pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin, osteonectin] in stimulated human whole saliva collected from 110 untreated dental patients. Alveolar bone loss scores for each patient were derived from radiographic examination. Variables positively associated with increased bone loss score were: age, current smoking, use of bisphosphonate drugs, and salivary interleukin-1beta levels above the median. Salivary osteonectin levels above the median were associated with a decreased bone loss score. Additional in vitro studies were carried out to determine the fate of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha added to whole and parotid saliva. All cytokines added to saliva were detected in significantly lower concentrations than when added to buffer alone. Protease inhibitors added to saliva did not prevent the reduction in detection of biomarkers. Variation in time of incubation, repeated cycles of freezing and thawing, or exposure to dimethylsulfoxide did not appreciably affect the measurement of cytokines in saliva. These results suggest that detection of biomarkers by conventional immunoassays may underestimate the actual quantity of molecules in saliva.


Ste2p Under the Microscope: the Investigation of Oligomeric States of a Yeast G Protein-Coupled Receptor.
Oligomerization of G protein-coupled receptors (GPCRs) may play important roles in maturation, internalization, signaling, and pharmacology of these receptors. However, the nature and extent of their oligomerization is still under debate. In our study, Ste2p, a yeast mating pheromone GPCR, was tagged with enhanced green fluorescent protein (EGFP), mCherry, and with split florescent protein fragments at the receptor C-terminus. The Förster resonance energy transfer (FRET) technique was used to detect receptors' oligomerization by calculating the energy transfer from EGFP to mCherry. Stimulation of Ste2p oligomers with the receptor ligand did not result in any significant change on observed FRET values. The bimolecular fluorescence complementation (BiFC) assay was combined with FRET to further investigate the tetrameric complexes of Ste2p. Our results suggest that in its quiescent (nonligand-activated) state, Ste2p is found at least as a tetrameric complex on the plasma membrane. Intriguingly, receptor tetramers in their active form showed a significant increase in FRET. This study provides a direct in vivo visualization of Ste2p tetramers and the pheromone effect on the extent of the receptor oligomerization.


[Hypothalamic control of ACTH secretion].
The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the alpha-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels.


[Determining the relative content of cisplatin in cells by acridine orange fluorescence intensity].
The fluorescence intensity of acridine orange (AO) dye bound to living human leukocytes, rat leukocytes, and Pliss lymphosarcoma cells of rat has been studied by fluorescence microscopy. The cell suspension of each test was divided into two parts, to one of which the drug cisplatin was added to a final concentration of 0.1 μg/mL and the mixture was incubated for 20 - 60 min. Acridine orange was then added and the average intensity of red and green fluorescence of cells was determined. The brightness of AO in the green region of the spectrum was reduced approximately 3-fold (p = 0.001) in cells with cisplatin. In the red region of the fluorescence, differences in the brightness of cells with and without cisplatin were not observed. These data indicate that a decrease in the brightness of green fluorescence of AO can be a test for the presence of cisplatin in cells.


Structural discrimination of networks by using distance, degree and eigenvalue-based measures.
In chemistry and computational biology, structural graph descriptors have been proven essential for characterizing the structure of chemical and biological networks. It has also been demonstrated that they are useful to derive empirical models for structure-oriented drug design. However, from a more general (complex network-oriented) point of view, investigating mathematical properties of structural descriptors, such as their uniqueness and structural interpretation, is also important for an in-depth understanding of the underlying methods. In this paper, we emphasize the evaluation of the uniqueness of distance, degree and eigenvalue-based measures. Among these are measures that have been recently investigated extensively. We report numerical results using chemical and exhaustively generated graphs and also investigate correlations between the measures.


In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors.
The identity of T-cell progenitors that seed the thymus has remained controversial, largely because many studies differ over whether these progenitors retain myeloid potential. Contradictory reports diverge in their use of various in vitro and in vivo assays. To consolidate these discordant findings, we compared the myeloid potential of 2 putative thymus seeding populations, common lymphoid progenitors (CLPs) and multipotent progenitors (MPPs), and the earliest intrathymic progenitor (DN1), using 2 in vitro assays and in vivo readouts. These assays gave contradictory results: CLP and DN1 displayed surprisingly robust myeloid potential on OP9-DL1 in vitro stromal cocultures but displayed little myeloid potential in vivo, as well as in methylcellulose cultures. MPP, on the other hand, displayed robust myeloid potential in all settings. We conclude that stromal cocultures reveal cryptic, but nonphysiologic, myeloid potentials of lymphoid progenitors, providing an explanation for contradictory findings in the field and underscoring the importance of using in vivo assays for the determination of physiologic lineage potentials.


Plexin-D1 is a novel regulator of germinal centers and humoral immune responses.
Long-lived humoral immune responses depend upon the generation of memory B cells and long-lived plasma cells during the germinal center (GC) reaction. These memory compartments, characterized by class-switched IgG and high-affinity Abs, are the basis for successful vaccination. We report that a new member of the plexin family of molecules, plexin-D1, controls the GC reaction and is required for secondary humoral immune responses. Plexin-D1 was not required for B cell maturation, marginal zone precursor development, dark and light zone formation, Igλ(+) and Igκ(+) B cell skewing, B1/B2 development, and the initial extrafollicular response. Plexin-D1 expression was increased following B cell activation, and PlxnD1(-/-) mice exhibited defective GC reactions during T-dependent immune activation. PlxnD1(-/-) B cells showed a defect in migration toward the GC chemokines, CXCL12, CXCL13, and CCL19. Accordingly, PlxnD1(-/-) mice exhibited defective production of IgG1 and IgG2b, but not IgG3 serum Ab, accompanied by reductions in long-lived bone marrow plasmacytes and recall humoral memory responses. These data show a new role for immune plexins in the GC reaction and generation of immunologic memory.


Raman spectrum matching with contrastive representation learning.
Raman spectroscopy is an important, low-cost, non-intrusive technique often used for chemical identification. Typical approaches identify a spectrum by comparing it with a reference database using supervised machine learning, which usually requires careful preprocessing and multiple spectra available per analyte. We propose a new machine learning technique for spectrum identification using contrastive representation learning. Our approach requires no preprocessing and works with as little as a single reference spectrum per analyte. We have significantly improved or are on par with the existing state-of-the-art analyte identification accuracy on two Raman spectral datasets and one SERS dataset that include a single component. We demonstrate that the identification accuracy can be further increased by slightly increasing the candidate set size using conformal prediction on the SERS dataset. Based on our findings, we believe contrastive representation learning is a promising alternative to the existing methods for Raman spectrum matching.


Advancing paternal age and simplex autism.
De novo events appear more common in female and simplex autism spectrum disorder (ASD) cases and may underlie greater ASD risk in older fathers' offspring. This study examined whether advancing paternal age predicts an increase in simplex (n = 90) versus multiplex ASD cases (n = 587) in 677 participants (340 families). Whether or not controlling for maternal age, results support a significant interaction of linear paternal age and sex of the child on simplex family type. Female ASD cases were significantly more likely to be simplex as paternal age increased, but the increase for males was not significant. Findings suggest that ASD arising from non-familial, de novo events may be far less prominent in males than in females, even if more prevalent in males, due to the substantially larger number of male cases attributable to other, more strongly male-biased risk factors.


A new approach for efficient genotype imputation using information from relatives.
Genotype imputation can help reduce genotyping costs particularly for implementation of genomic selection. In applications entailing large populations, recovering the genotypes of untyped loci using information from reference individuals that were genotyped with a higher density panel is computationally challenging. Popular imputation methods are based upon the Hidden Markov model and have computational constraints due to an intensive sampling process. A fast, deterministic approach, which makes use of both family and population information, is presented here. All individuals are related and, therefore, share haplotypes which may differ in length and frequency based on their relationships. The method starts with family imputation if pedigree information is available, and then exploits close relationships by searching for long haplotype matches in the reference group using overlapping sliding windows. The search continues as the window size is shrunk in each chromosome sweep in order to capture more distant relationships. The proposed method gave higher or similar imputation accuracy than Beagle and Impute2 in cattle data sets when all available information was used. When close relatives of target individuals were present in the reference group, the method resulted in higher accuracy compared to the other two methods even when the pedigree was not used. Rare variants were also imputed with higher accuracy. Finally, computing requirements were considerably lower than those of Beagle and Impute2. The presented method took 28 minutes to impute from 6 k to 50 k genotypes for 2,000 individuals with a reference size of 64,429 individuals. The proposed method efficiently makes use of information from close and distant relatives for accurate genotype imputation. In addition to its high imputation accuracy, the method is fast, owing to its deterministic nature and, therefore, it can easily be used in large data sets where the use of other methods is impractical.


[Autogenic training as a complementary therapy in unstable arterial hypertension in chronic uremics under periodic dialysis].
Consideration of the precarious mental balance of chronic uraemic patients receiving periodic haemodialysis, which often affects arterial pressure, led to a group of such patients being subjected to additional treatment in the form of Autogenous Training (A.T.). Comparison of some parameters such as arterial pressure and ECG's evaluated before and after A.T. shows, in several cases, a noticeable clinical improvement. It also has a definite tranquillising effect on the general anxiety state, which makes for better and longer-lasting adaptation to periodic dialysis. In the light of these results, Autogenous Training is proposed as a complementary treatment system for obviating certain non-physiological aspects of dialysis.


Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow.
The current study was performed to determine whether baroreflex resetting after acute administration of converting enzyme inhibitors (CEIs) was dependent on the concomitant decrease in mean arterial pressure (MAP). Reflex changes in lumbar sympathetic nerve activity (LSNA) due to increases and decreases in MAP [i.v. phenylephrine (PE) and nitroprusside infusions] were determined in normotensive and renal hypertensive (1-kidney, 1-clip) anesthetized WKY rats 1) before (control), 2) 15 min after intravenous captopril (2 mg/kg) or enalaprilat (300 micrograms), and 3) 15 min after MAP was returned to pre-CEI levels with intravenous PE. CEIs decreased MAP and caused a leftward shift of the MAP-LSNA curve toward a lower operating pressure range in all hypertensive and in one group of normotensive rats. The baroreflex curve remained shifted to the left even after MAP was restored to pre-CEI levels by infusion of PE. Thus CEIs cause a pressure-independent resetting of baroreflex control of sympathetic outflow within 15 min. This effect of CEIs is most likely due to elimination of a central nervous system effect of circulating angiotensin II and could contribute to the antihypertensive actions of this class of compounds.


A NIR fluorescent probe for the detection of fluoride ions and its application in in vivo bioimaging.
A novel near-infrared (NIR) fluorescent probe for the detection of fluoride ions has been developed, which is based on the F-triggered cleavage reaction of the Si-O bond. This probe exhibits excellent selectivity and sensitivity towards fluoride ions. The results of bioimaging experiments with HepG2 cells and mice show that the fluoride probe is available for visualizing exogenous fluoride ions in vitro and in vivo.


Comparison of Neurovascular Characteristics of Facial Skin in Patients After Primary and Revision Rhytidectomies.
Wound healing influences both the cosmetic and functional outcomes of facial surgery. Study of cutaneous innervation may afford insight into patients' preoperative wound healing potential and aid in their selection of appropriate surgical procedures. To present the quantitative and qualitative differences of epidermal nerve fibers (ENFs), neurotransmitters, vasculature, and mast cells in facial skin among patients after primary and revision rhytidectomies. This pilot study collected cutaneous specimens from 8 female patients aged 42 to 66 years who underwent primary rhytidectomy (n = 5) and revision rhytidectomy (n = 3) at Centennial Lakes Surgery Center, Edina, Minnesota, from July 2010 to March 2014. Tissue was processed for confocal/epifluorescence microscopy and indirect immunofluorescent localization of several neural and tissue antigens as well as basement membrane and mast cell markers. Primary rhytidectomy vs revision rhytidectomy with selection of a small area of redundant, otherwise disposed of tissue anterior to the tragus for ENF study. Demographic characteristics included smoking status; 10-point rating scales for facial sensation, pain, and paresthesias; and confocal/epifluorescence microscopy to quantify ENFs, neurotransmitters, vasculature, and mast cells. Patients in the primary rhytidectomy group had a mean (SD) of 54.4 (31.6) ENFs/mm (range, 14.2-99.2 ENFs/mm), and those in the revision rhytidectomy group had a mean (SD) of 18.6 (5.8) ENFs/mm (range, 13.8-25.0 ENFs/mm). A patient in the primary rhytidectomy group was a 25-pack-year smoker and had 14.2 ENFs/mm, the lowest in both groups. In addition to these structural neural changes, functional neural changes in revision rhytidectomy samples included qualitative changes in normal neural antigen prevalence (substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide). Capillary loops appeared less robust and were less common in dermal papilla among samples from both the primary and revision groups, and mast cells were more degranulated. No differences were found in subjective, self-reported postoperative facial sensation. Previous skin elevation was associated with decreased epidermal nerve fiber density and qualitative changes in dermal nerves, capillaries, and mast cells in a clinical sample of patients undergoing rhytidectomy. Future research is needed to determine whether histological findings predict wound healing and to better understand the effects of surgery on regenerative capacity of epidermal nerve fibers. NA.


Function and regulation of Rnd proteins in cortical projection neuron migration.
The mammalian cerebral cortex contains a high variety of neuronal subtypes that acquire precise spatial locations and form long or short-range connections to establish functional neuronal circuits. During embryonic development, cortical projection neurons are generated in the areas lining the lateral ventricles and they subsequently undergo radial migration to reach the position of their final maturation within the cortical plate. The control of the neuroblast migratory behavior and the coordination of the migration process with other neurogenic events such as cell cycle exit, differentiation and final maturation are crucial to normal brain development. Among the key regulators of cortical neuron migration, the small GTP binding proteins of the Rho family and the atypical Rnd members play important roles in integrating intracellular signaling pathways into changes in cytoskeletal dynamics and motility behavior. Here we review the role of Rnd proteins during cortical neuronal migration and we discuss both the upstream mechanisms that regulate Rnd protein activity and the downstream molecular pathways that mediate Rnd effects on cell cytoskeleton.


Exploring communication of traumatic experiences from Khmer Rouge genocide survivors to their offspring: In-depth interviews with both generations.
Traumatic events experienced by parents who have survived genocide influence mental health among their offspring. This study aims at exploring how the communication of traumatic events between Khmer Rouge survivors and their offspring was perceived by both generations. Qualitative interviews were performed with six Khmer Rouge survivors and with six young people representing the second generation and were analysed using a content analysis approach. Parents felt that informing their children was important to instill gratitude for living a better life and to empower them. Among children, this was met with empathy but sometimes also disbelief and at times they blamed their parents for being too submissive. The study discloses the complexity, pros and cons of intergenerational sharing of trauma.


Survival differences in rheumatoid arthritis interstitial lung disease and idiopathic pulmonary fibrosis may be explained by delays in presentation: results from multivariate analysis in a monocentric UK study.
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) has a better prognosis compared to idiopathic pulmonary fibrosis (IPF). Recent data suggest that antifibrotics are effective in slowing progression across both groups. Hence, we designed this study to investigate the similarities and differences between these groups of patients. This is a retrospective cohort study examining baseline data, progression and outcomes in patients with RA-ILD and IPF prior to antifibrotic use in the Coventry ILD database. Ethics approval was obtained from the University Hospital Coventry and Warwickshire NHS Trust. Statistical analysis was performed using R software and Cox's proportional hazards technique was used for survival analysis. We identified 131 cases, including 49 patients with IPF, 34 patients with RA-ILD and 48 patients with other forms of idiopathic interstitial pneumonia. At baseline, there were significant differences in the groups with RA-ILD patients being significantly younger (65.7 vs 72.4 years), had preserved lung volumes (FVC 95% vs 84.7%) and higher gas transfer (61.5% vs 48.2%) compared to IPF patients. 5-year survival was better for RA-ILD compared to IPF (87.5% vs 40.4%, p = 0.0042). Univariate analysis revealed gas transfer, FVC, age, sex and phenotype (IPF or RA-ILD) were all significant predictors, but multivariate analysis revealed that gas transfer and age were both significantly associated with prognosis, whereas sex, FVC or phenotype were not significant. This study suggests that the difference between RA-ILD and IPF prognosis may be due to demographics and early diagnosis rather than the diseases behaving differently. This has important management implications.


Flagella-related gene mutations in Vibrio cholerae during extended cultivation in nutrient-limited media impair cell motility and prolong culturability.
Vibrio cholerae undergoes a transition to a viable but non-culturable (VNC) state when subjected to various environmental stresses. We showed here that flagellar motility was involved in the development of the VNC state of V. cholerae. In this study, motility-defective isolates with mutations in various flagella-related genes, but not motile isolates, were predominantly obtained under the stress of long-term batch culture. Other genomic regions were highly conserved, suggesting that the mutations were selective. During the stationary phase of long-term culture, V. cholerae isolates with mutations in the acetate kinase and flagella-related genes were predominant. This study suggests that genes involved in specific functions in V. cholerae undergo mutations under certain environmental conditions.


Mutation of the glycine residue preceding the sixth tyrosine of the LAT adaptor severely alters T cell development and activation.
The LAT transmembrane adaptor is essential to transduce intracellular signals triggered by the TCR. Phosphorylation of its four C-terminal tyrosine residues (136, 175, 195, and 235 in mouse LAT) recruits several proteins resulting in the assembly of the LAT signalosome. Among those tyrosine residues, the one found at position 136 of mouse LAT plays a critical role for T cell development and activation. The kinetics of phosphorylation of this residue is delayed as compared to the three other C-terminal tyrosines due to a conserved glycine residue found at position 135. Mutation of this glycine into an aspartate residue (denoted LATG135D) increased TCR signaling and altered antigen recognition in human Jurkat T cells and ex vivo mouse T cells. Here, using a strain of LATG135D knockin mice, we showed that the LATG135D mutation modifies thymic development, causing an increase in the percentage of CD4+CD8+ double-positive cells, and a reduction in the percentage of CD4+ and CD8+ single-positive cells. Interestingly, the LATG135D mutation alters thymic development even in a heterozygous state. In the periphery, the LATG135D mutation reduces the percentage of CD8+ T cells and results in a small increment of γδ T cells. Remarkably, the LATG135D mutation dramatically increases the percentage of central memory CD8+ T cells. Finally, analysis of the proliferation and activation of T lymphocytes shows increased responses of T cells from mutant mice. Altogether, our results reinforce the view that the residue preceding Tyr136 of LAT constitutes a crucial checkpoint in T cell development and activation.


LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes.
Epidemiological studies have shown that abnormalities of glucose metabolism are involved in leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). However, the physiological significance of this association is unclear. In the present study, we investigated the effect of LRRK2 on high-fat diet (HFD)-induced glucose intolerance using Lrrk2-knockout (KO) mice. We found for the first time that HFD-fed KO mice display improved glucose tolerance compared with their wild-type (WT) counterparts. In addition, high serum insulin and leptin, as well as low serum adiponectin resulting from HFD in WT mice were improved in KO mice. Using western blotting, we found that Lrrk2 is highly expressed in adipose tissues compared with other insulin-related tissues that are thought to be important in glucose tolerance, including skeletal muscle, liver, and pancreas. Lrrk2 expression and phosphorylation of its kinase substrates Rab8a and Rab10 were significantly elevated after HFD treatment in WT mice. In cell culture experiments, treatment with a LRRK2 kinase inhibitor stimulated insulin-dependent membrane translocation of glucose transporter 4 (Glut4) and glucose uptake in mouse 3T3-L1 adipocytes. We conclude that increased LRRK2 kinase activity in adipose tissue exacerbates glucose tolerance by suppressing Rab8- and Rab10-mediated GLUT4 membrane translocation.


Isolation and characterization of genomic clones corresponding to the human type II procollagen gene.
A recombinant human DNA library was screened using probes corresponding to the chick alpha 1 (II) procollagen gene. This resulted in the isolation of 2 different genomic clones, LgHCol(II)a and LgHCol(II)b. LgHCol(II)a was identified as corresponding to the alpha 1(II) gene by comparative hybridization and DNA sequence analysis. DNA sequence established that LgHCol(II)a extends at least from amino acid 694 of the triple helix through 54 amino acids of the COOH-propeptide. Hybridization with a probe containing only the exon at the 3' end of the chicken gene suggests that the clone contains the 3' end of the human gene. Thus LgHCol(II)a contains approximately 40% of the coding sequences of the human type II collagen gene.


Cu-Based Thermocompression Bonding and Cu/Dielectric Hybrid Bonding for Three-Dimensional Integrated Circuits (3D ICs) Application.
Advanced packaging technology has become more and more important in the semiconductor industry because of the benefits of higher I/O density compared to conventional soldering technology. In advanced packaging technology, copper-copper (Cu-Cu) bonding has become the preferred choice due to its excellent electrical and thermal properties. However, one of the major challenges of Cu-Cu bonding is the high thermal budget of the bonding process caused by Cu oxidation, which can result in wafer warpage and other back-end-of-line process issues in some cases. Thus, for specific applications, reducing the thermal budget and preventing Cu oxidation are important considerations in low-temperature hybrid bonding processes. This paper first reviews the advancements in low-temperature Cu-based bonding technologies for advanced packaging. Various low-temperature Cu-Cu bonding techniques such as surface pretreatment, surface activation, structure modification, and orientation control have been proposed and investigated. To overcome coplanarity issues of Cu pillars and insufficient gaps for filling, low-temperature Cu-Cu bonding used, but it is still challenging in fine-pitch applications. Therefore, low-temperature Cu/SiO2, Cu/SiCN, and Cu/polymer hybrid bonding have been developed for advanced packaging applications. Furthermore, we present a novel hybrid bonding scheme for metal/polymer interfaces that achieves good flatness and an excellent bonding interface without the need for the chemical mechanical polishing (CMP) process.


Spongivory in hawksbill turtles: a diet of glass.
The hawksbill(Eretmochelys imbricata), an endangered marine turtle associated with coral reefs throughout the tropics, feeds almost exclusively on sponges in the Caribbean, and possibly throughout its range. It is one of fewer than a dozen vertebrates that are known to specialize on this widely distributed but well-defended food resource. The diet is taxonomically narrow and highly uniform geographically, includes sponges that are toxic to other vertebrates, and contains more silica than that of other vertebrates. By affecting space competition, spongivory by hawksbills may influence succession and diversity of reef communities.


High-risk breast lesions at imaging-guided needle biopsy: usefulness of MRI for treatment decision.
The purpose of this study is to evaluate the role of MRI for characterization of high-risk breast lesions diagnosed at imaging-guided needle biopsy. In this retrospective analysis of 220 patients, 227 high-risk lesions (94 papillomas, 64 radial sclerosing lesions, 46 lobular neoplasias, and 23 atypical ductal hyperplasias) found at 11-gauge vacuum-assisted or 14-gauge needle biopsy were studied with dynamic MRI (time resolution, 84 or 88 seconds; gadopentetate dimeglumine or gadobenate dimeglumine, 0.1 mmol/kg). When lesions showed contrast enhancement on subtracted images, they were considered suspicious for malignancy. The reference standard was histopathologic examination after surgical excision in 190 of 227 (84%) lesions and negative follow-up (≥ 24 months) in 37 of 227 (16%) lesions. Predictive values and likelihood ratios were calculated. Of 227 lesions, 155 (68%) were contrast enhancing and 72 (32%) were not. Of 155 contrast-enhancing lesions, 28 (18%) were upgraded to malignancy after surgical excision (nine papillomas, one radial sclerosing lesion, 11 lobular neoplasias, and seven atypical ductal hyperplasias); there were 11 invasive carcinomas and 17 ductal carcinomas in situ, four of the latter being G3. Of 72 non-contrast-enhancing lesions, two (3%) were upgraded to malignancy after surgical excision (one radial sclerosing lesion and one lobular neoplasia), both of which were G1 ductal carcinoma in situ. Cancer probability was significantly higher for contrast-enhancing (18%) than for non-contrast-enhancing (3%) lesions (p = 0.001) and for nonmasslike (43%) than for masslike (14%) lesions (p = 0.005). The positive predictive value was 18% (28/155; 95% CI, 13-24%), the negative predictive value was 97% (70/72; 95% CI, 94-99%), the positive likelihood ratio was 1.448 (95% CI, 1.172-1.788), and the negative likelihood ratio was 0.188 (95% CI, 0.152-0.232). The absence of enhancement at dynamic MRI allowed reliable exclusion of invasive cancers among high-risk lesions diagnosed at needle biopsy.


The right to refuse treatment: why psychiatrists should and can make it work.
There is a right to refuse treatment and this right already exists in the legal doctrine of informed consent. The basic legal justification for overcoming this right is the incompetence of the patient. Incompetence is also the central consideration in overcoming any constitutional right to refuse treatment. The constitutional theories of the right to refuse treatment are briefly presented and their implementation in different recent decisions is considered. A distinction is made between the requirement of proving incompetency and the requirement of appointing a neutral party as arbiter for incompetent patients. A recent constitutional ruling that recognizes this distinction and permits psychiatrists rather than neutral arbiters to make treatment decisions for patients is discussed as a model that should be acceptable to psychiatry.


Insight into SARS-CoV-2 Omicron variants in Saudi Arabian genomic isolates.
To investigate the emergent mutations involved in the evolutionary stages of the virus for better management of pandemic. This cross-sectional genomic investigation was performed on February 28, 2022, at the Biology Department, Faculty of Science, Tabuk University. Numerous mutations were searched in genomic isolates of Omicron variant prevalent in the Kingdom of Saudi Arabian. Whole-genome sequences were retrieved from genomic databases and were subjected to the Global Initiative on Sharing Avian Influenza Data (GISAID) CoVsurver for the Omicron variant detection and mutations. Approximately 8.755 million SARS-CoV-2 genomes were reported to GISAID on February 28, 2022, of which 1270 have been reported from the Kingdom of Saudi Arabia. Among the 1270 genomes, 30 were Omicron variants. Among the Saudi Arabian genomes, 30 were detected as Omicron variants. Twenty-four unique mutations have been detected in membrane, envelope, spike and non-structural proteins (NSP) 12, NSP3, and NSP2. Ten of these unique mutations have been detected in spike protein. The current study provides useful information for further experimental investigation of mutation's effects on virus transmission, severity, and vaccine efficacy.


Function of upper esophageal sphincter during swallowing: the grabbing effect.
This study investigated deglutitive axial force developed within the pharynx, upper esophageal sphincter (UES), and cervical esophagus. Position and deglutitive excursion of the UES were determined using combined manometry and videofluoroscopy in eight healthy volunteers. Deglutitive clearing force was quantified with a force transducer to which nylon balls of 6- or 8-mm diameter were tethered and positioned within the oropharynx, hypopharynx, UES, and cervical esophagus. Axial force recordings were synchronized with videofluoroscopic imaging. Clearing force was dependent on both sphere diameter (P < 0.05) and location, with greater force exhibited in the hypopharynx and UES compared with the oropharynx and esophagus (P < 0.05). Within the UES, the onset of traction force coincided with passage of the pharyngeal clearing wave but persisted well beyond this. On videofluoroscopy, the persistent force was associated with the aboral motion of the ball caught within the UES. Force abated with gradual slippage of the UES around the ball. The force attributable to the combination of UES contraction and laryngeal descent was named the grabbing effect. The grabbing effect functions to transfer luminal contents distal to the laryngeal inlet at the end of the pharyngeal swallow, presumably acting to prevent regurgitation and/or aspiration of swallowed material.


Analysis of maternal effect mutant combinations elucidates regulation and function of the overlap of hunchback and Krüppel gene expression in the Drosophila blastoderm embryo.
The metameric organisation of the Drosophila embryo is generated early during development, due to the action of maternal effect and zygotic segmentation and homeotic genes. The gap genes participate in the complex process of pattern formation by providing a link between the maternal and the zygotic gene activities. Under the influence of maternal gene products they become expressed in distinct domains along the anteroposterior axis of the embryo; negative interactions between neighboring gap genes are thought to be involved in establishing the expression domains. The gap gene activities in turn are required for the correct patterning of the pair-rule genes; little is known, however, about the underlying mechanisms. We have monitored the distribution of gap and pair-rule genes in wild-type embryos and in embryos in which the anteroposterior body pattern is greatly simplified due to combinations of maternal effect mutations (staufen exuperantia, vasa exuperantia, vasa exuperantia, bicoid oskar, bicoid oskar torsolike, vasa torso exuperantia). We show that the domains of protein distribution of the gap genes hunchback and Krüppel overlap in wild-type embryos. Based on the analysis of the maternal mutant combinations, we suggest an explanation of how this overlap is generated. Furthermore, our data show that different constellations of gap gene activities provide different input for the pair-rule genes, and thus strongly suggest that the overlap of hunchback and Krüppel in wild-type is functional in the formation of the patterns of pair-rule genes.


Using multivariate statistical methods to model the electrospray ionization response of GXG tripeptides based on multiple physicochemical parameters.
Response factors were determined for twelve GXG peptides (where G stands for glycine and X is any of alanine [A], arginine [R], asparagine [N], aspartic acid [D], glycine [G], histidine [H], leucine [L], lysine [K], phenylalanine [F], serine [S], tyrosine [Y], valine [V]) by electrospray ionization mass spectrometry (ESI-MS). The response factors were measured using a novel flow injection method. This new method is based on the Gaussian distribution of analyte concentration resulting from band-broadening dispersion experienced by the analyte upon passage through an extended volume of PEEK tubing. This method removes the need for preparing a discrete series of standard solutions to assess concentration-dependent response. Relative response factors were calculated for each peptide with reference to GGG. The observed trends in the relative response factors were correlated with several analyte physicochemical parameters, chosen based on current understanding of ion release from charged droplets during the ESI process. These include analyte properties: nonpolar surface area; polar surface area; gas-phase basicity; proton affinity; and Log D. Multivariate statistical analysis using multiple linear regression, decision tree, and support vector regression models were investigated to assess their potential for predicting ESI response based on the analyte properties. The support vector regression model was more versatile and produced the least predictive error following 12-fold cross-validation. The effect of variation in solution pH on the relative response factors is highlighted, as evidenced by the different predictive models obtained for peptide response at two pH values (pH = 6.0 and 9.0). The relationship between physicochemical parameters and associated ionization efficiencies for GXG tripeptides is discussed based on the equilibrium partitioning model.


Does abstaining from alcohol in high school moderate intervention effects for college students? Implications for tiered intervention strategies.
Brief motivational intervention (BMI) and personalized feedback intervention (PFI) are individual-focused brief alcohol intervention approaches that have been proven efficacious for reducing alcohol use among college students and young adults. Although the efficacy of these two intervention approaches has been well established, little is known about the factors that may modify their effects on alcohol outcomes. In particular, high school drinking may be a risk factor for continued and heightened use of alcohol in college, and thus may influence the outcomes of BMI and PFI. The purpose of this study was to investigate whether high school drinking was associated with different intervention outcomes among students who received PFI compared to those who received BMI. We conducted moderation analyses examining 348 mandated students (60.1% male; 73.3% White; and 61.5% first-year student) who were randomly assigned to either a BMI or a PFI and whose alcohol consumption was assessed at 4-month and 15-month follow-ups. Results from marginalized zero-inflated Poisson models showed that high school drinking moderated the effects of PFI and BMI at the 4-month follow-up but not at the 15-month follow-up. Specifically, students who reported no drinking in their senior year of high school consumed a 49% higher mean number of drinks after receiving BMI than PFI at the 4-month follow-up. The results suggest that alcohol consumption in high school may be informative when screening and allocating students to appropriate alcohol interventions to meet their different needs.


New anthracycline antibiotics, auramycins and sulfurmycins. II. Isolation and characterization of 10 minor components (C approximately G).
Following the discovery of new anthracycline antibiotics, auramycins A and B and sulfurmycins A and B, we found 10 minor analogues of auramycins and sulfurmycins, C, D, E, F and G, from the culture broth of a mutant strain of Streptomyces galilaeus OBB-111 and prepared 2 analogues as the chemical derivatives from auramycin G and sulfurmycin G. All analogues have a sugar moiety at C-7 position of the aglycones. These analogues exhibit activities against Gram-positive bacteria and P388 leukemia.


High-resolution computed tomographic characteristics in acute farmer's lung and in its follow-up.
High resolution computed tomography (HRCT) scans are increasingly used in hypersensitivity pneumonitis (HP). This study looked at HRCT findings at different phases of farmer's lung (FL), a common form of HP. A cross sectional analysis of 95 HRCT scans of FL cases (20 acute, 75 with a history of FL, 48 still in contact (Ex +) (dairy farm), and 27 who had ceased contact (Ex-)) was made. All scans were read independently by two, and if needed by three, radiologists blinded to the category. The lungs were divided into six regions (fives lobes + lingula), and read for attenuation/mosaic, ground-glass, micronodules, fibrosis, and emphysema. A score of 0-3 was given for each region and each variable: 0 = absence, 1 =<25% of the surface, 2 = 25-50%, 3 =>50%. Mediastinal lymphadenopathy was also noted. Ground glass, predominating in the lower lobes, was the most frequent feature in the acute and Ex+ cases. Other abnormalities had no preferential distribution. Ex+ had more ground-glass than the Ex- (p=0.0025). Emphysema was more frequently seen than interstitial fibrosis (p=0.004). Mediastinal lymphadenopathy was present in 26 cases (9 acute, 10 Ex+ and 7 Ex-). In conclusion, in farmer's lung: 1) ground-glass predominates in the lower lobes while the other abnormalities have no anatomic predilection; 2) contact avoidance allows a better resolution of computed tomography abnormalities than continued exposure; 3) emphysema is a more frequent finding than interstitial fibrosis; and 4) the presence of mediastinal lymphadenopathy has no negative diagnostic value.


Bookmarking promoters in mitotic chromatin: poly(ADP-ribose)polymerase-1 as an epigenetic mark.
Epigenetics are the heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. After mitosis, it is thought that bookmarking transcription factors remain at promoters, regulating which genes become active and which remain silent. Herein, we demonstrate that poly(ADP-ribose)polymerase-1 (PARP-1) is a genome-wide epigenetic memory mark in mitotic chromatin, and we further show that the presence of PARP-1 is absolutely crucial for reactivation of transcription after mitosis. Based on these findings, a novel molecular model of epigenetic memory transmission through the cell cycle is proposed.


Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United States.
AbstractThe safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01E or AS03B), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18-39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo. The response to a third dose was evaluated in a subset of nine participants remote from primary vaccination. Humoral immunogenicity was assessed using a 50% microneutralization assay. All DPIV formulations were well tolerated. No vaccine-related serious adverse events were observed through 12 months after the second vaccine dose. In all DPIV groups, geometric mean antibody titers peaked at Day 56, waned through 6 months after the second vaccine dose, and then stabilized. In the nine subjects where boosting was evaluated, a strong anamnestic response was observed. These results support continuation of the clinical development of this dengue vaccine candidate (clinicaltrials.gov: NCT01666652).


Post-transition state dynamics and product energy partitioning following thermal excitation of the F⋯HCH2CN transition state: Disagreement with experiment.
Born-Oppenheimer direct dynamics simulations were performed to study atomistic details of the F + CH3CN → HF + CH2CN H-atom abstraction reaction. The simulation trajectories were calculated with a combined M06-2X/MP2 algorithm utilizing the 6-311++G** basis set. The experiments were performed at 300 K, and assuming the accuracy of transition state theory (TST), the trajectories were initiated at the F⋯HCH2CN abstraction TS with a 300 K Boltzmann distribution of energy and directed towards products. Recrossing of the TS was negligible, confirming the accuracy of TST. HF formation was rapid, occurring within 0.014 ps of the trajectory initiation. The intrinsic reaction coordinate (IRC) for reaction involves rotation of HF about CH2CN and then trapping in the CH2CN⋯HF post-reaction potential energy well of ∼10 kcal/mol with respect to the HF + CH2CN products. In contrast to this IRC, five different trajectory types were observed: the majority proceeded by direct H-atom transfer and only 11% approximately following the IRC. The HF vibrational and rotational quantum numbers, n and J, were calculated when HF was initially formed and they increase as potential energy is released in forming the HF + CH2CN products. The population of the HF product vibrational states is only in qualitative agreement with experiment, with the simulations showing depressed and enhanced populations of the n = 1 and 2 states as compared to experiment. Simulations with an anharmonic zero-point energy constraint gave product distributions for relative translation, HF rotation, HF vibration, CH2CN rotation, and CH2CN vibration as 5%, 11%, 60%, 7%, and 16%, respectively. In contrast, the experimental energy partitioning percentages to HF rotation and vibration are 6% and 41%. Comparisons are made between the current simulation and those for other F + H-atom abstraction reactions. The simulation product energy partitioning and HF vibrational population for F + CH3CN → HF + CH2CN resemble those for other reactions. A detailed discussion is given of possible origins of the difference between the simulation and experimental energy partitioning dynamics for F + CH3CN → HF + CH2CN. The F + CH3CN reaction also forms the CH3C(F)N intermediate, in which the F-atom adds to the C≡N bond. However, this intermediate and F⋯CH3CN and CH3CN⋯F van der Waals complexes are not expected to affect the F + CH3CN → HF + CH2CN product energy partitioning.


[Preparation of a manual treatment of pressure ulcers which draws attention to moisture of the affected part].
As for pressure ulcers care, prevention is the most important approach. However, pressure ulcers, might develop despite enough care, depending on each person's physical condition. As for the treatment of pressure ulcers, maintenance of a moderately moist environment (60-70%) is quite important. We propose the use of ointment to control the moisture of a pressure ulcer environment. One ointment base absorbs moisture, while another provides moisture. We have prepared a manual that allows the user to select the medicine according to the degree of moisture of the affected part. When the moisture cannot be regulated with one ointment, it can be adjusted by mixing two or more ointments. In choosing a drug for external use, it is important to pay attention not only to the effect of the main ingredient but also to the physicochemical properties of the ointment base that serves as vehicle for that active component.


Genetic engineering of the glyoxalase pathway in tobacco leads to enhanced salinity tolerance.
The glyoxalase pathway involving glyoxalase I (gly I) and glyoxalase II (gly II) enzymes is required for glutathione-based detoxification of methylglyoxal. We had earlier indicated the potential of gly I as a probable candidate gene in conferring salinity tolerance. We report here that overexpression of gly I+II together confers improved salinity tolerance, thus offering another effective strategy for manipulating stress tolerance in crop plants. We have overexpressed the gly II gene either alone in untransformed plants or with gly I transgenic background. Both types of these transgenic plants stably expressed the foreign protein, and the enzyme activity was also higher. Compared with nontransformants, several independent gly II transgenic lines showed improved capability for tolerating exposure to high methylglyoxal and NaCl concentration and were able to grow, flower, and set normal viable seeds under continuous salinity stress conditions. Importantly, the double transgenic lines always showed a better response than either of the single gene-transformed lines and WT plants under salinity stress. Ionic measurements revealed higher accumulation of Na+ and K+ in old leaves and negligible accumulation of Na+ in seeds of transgenic lines as compared with the WT plants. Comparison of various growth parameters and seed production demonstrated that there is hardly any yield penalty in the double transgenics under nonstress conditions and that these plants suffered only 5% loss in total productivity when grown in 200 mM NaCl. These findings establish the potential of manipulation of the glyoxalase pathway for increased salinity tolerance without affecting yield in crop plants.


US-elastography in the differential diagnosis of benign and malignant thyroid nodules.
Ultrasound (US)-elastography is a newly developed imaging technique for the reconstruction of tissue stiffness by measuring the degree of tissue's deformation in response to the application of an external force. This technique has previously been shown to be useful in the differential diagnosis between benign and malignant tumors. The objective of this study was to assess the diagnostic accuracy of US-elastography in the differential diagnosis of thyroid cancer, using the cytologic/histopathologic analysis as the reference standard. A total of 67 consecutive patients with thyroid nodules who were referred to the Thyroid Unit at the Policlinico MultiMedica were enrolled in this prospective study between January and December 2006. Eighty-six nodules in these patients were examined by US B-mode, US color-power-Doppler, and US-elastography. Nodules were subjected to fine-needle aspiration biopsy and patients with a reading of malignant or indeterminate had thyroid surgery. The final diagnosis was based on the cytology reading in those who did not have surgery and the histopathology reading in those who had surgery. US-elastography scores were based on four classes of tissue stiffness (class 1 for soft nodules; class 2 and 3 for nodules with an intermediate degree of stiffness; class 4 for anelastic lesions). Seventeen nodules were malignant and 69 were benign. Sensitivity and specificity of the US-elastography for thyroid cancer diagnosis were 94.1% (16/17) and 81% (56/69), respectively. The positive and negative predictive values were 55.2% (16/29) and 98.2% (56/57), respectively. The accuracy of the technique was 83.7%. US-elastography is a promising technique that, combined with other US modalities, is easy and rapid to perform and can help to identify thyroid nodules that are likely to be malignant. An important limitation is probably lack of sensitivity for follicular thyroid carcinoma.


Human lung hydrolases delineate Mycobacterium tuberculosis-macrophage interactions and the capacity to control infection.
Pulmonary surfactant contains homeostatic and antimicrobial hydrolases. When Mycobacterium tuberculosis is initially deposited in the terminal bronchioles and alveoli, as well as following release from lysed macrophages, bacilli are in intimate contact with these lung surfactant hydrolases. We identified and measured several hydrolases in human alveolar lining fluid and lung tissue that, at their physiological concentrations, dramatically modified the M. tuberculosis cell envelope. Independent of their action time (15 min to 12 h), the effects of the hydrolases on the M. tuberculosis cell envelope resulted in a significant decrease (60-80%) in M. tuberculosis association with, and intracellular growth of the bacteria within, human macrophages. The cell envelope-modifying effects of the hydrolases also led to altered M. tuberculosis intracellular trafficking and induced a protective proinflammatory response to infection. These findings add a new concept to our understanding of M. tuberculosis-macrophage interactions (i.e., the impact of lung surfactant hydrolases on M. tuberculosis infection).


N-cadherin regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus in vivo.
N-Cadherin and β-catenin form a transsynaptic adhesion complex required for spine and synapse development. In adulthood, N-cadherin mediates persistent synaptic plasticity, but whether the role of N-cadherin at mature synapses is similar to that at developing synapses is unclear. To address this, we conditionally ablated N-cadherin from excitatory forebrain synapses in mice starting in late postnatal life and examined hippocampal structure and function in adulthood. In the absence of N-cadherin, β-catenin levels were reduced, but numbers of excitatory synapses were unchanged, and there was no impact on number or shape of dendrites or spines. However, the composition of synaptic molecules was altered. Levels of GluA1 and its scaffolding protein PSD95 were diminished and the density of immunolabeled puncta was decreased, without effects on other glutamate receptors and their scaffolding proteins. Additionally, loss of N-cadherin at excitatory synapses triggered increases in the density of markers for inhibitory synapses and decreased severity of hippocampal seizures. Finally, adult mutant mice were profoundly impaired in hippocampal-dependent memory for spatial episodes. These results demonstrate a novel function for the N-cadherin/β-catenin complex in regulating ionotropic receptor composition of excitatory synapses, an appropriate balance of excitatory and inhibitory synaptic proteins and the maintenance of neural circuitry necessary to generate flexible yet persistent cognitive and synaptic function.


Contrast-enhanced ultrasound with dispersion analysis for the localization of prostate cancer: correlation with radical prostatectomy specimens.
To determine the value of two-dimensional (2D) contrast-enhanced ultrasound (CEUS) imaging and the additional value of contrast ultrasound dispersion imaging (CUDI) for the localization of clinically significant prostate cancer (csPCa). In this multicentre study, subjects scheduled for a radical prostatectomy underwent 2D CEUS imaging preoperatively. CUDI maps were generated from the CEUS recordings. Both CEUS recordings and CUDI maps were scored on the likelihood of presenting csPCa (any Gleason ≥ 4 + 3 and Gleason 3 + 4 larger than 0.5 mL) by five observers and compared to radical prostatectomy histopathology. An automated three-dimensional (3D) fusion protocol was used to match imaging with histopathology. Receiver operator curve (ROC) analysis was performed per observer and imaging modality. 133 of 216 (62%) patients were included in the final analysis. Average area under the ROC for all five readers for CEUS, CUDI and the combination was 0.78, 0.79 and 0.78, respectively. This yields a sensitivity and specificity of 81 and 64% for CEUS, 83 and 56% for CUDI and 83 and 55% for the combination. Interobserver agreement for CEUS, CUDI and the combination showed kappa values of 0.20, 0.18 and 0.18 respectively. The sensitivity and specificity of 2D CEUS and CUDI for csPCa localization are moderate. Despite compressing CEUS in one image, CUDI showed a similar performance to 2D CEUS. With a sensitivity of 83% at cutoff point 3, it could become a useful imaging procedure, especially with 4D acquisition, improved quantification and combination with other US imaging techniques such as elastography.


Ectopic expression of the NtSET1 histone methyltransferase inhibits cell expansion, and affects cell division and differentiation in tobacco plants.
The tobacco NtSET1 gene encodes a member of the SUV39H family of histone methyltransferases. Ectopic expression of NtSET1 causes an increase in methylated histone H3 lysine 9 and abnormal chromosome segregation in tobacco suspension cells, and inhibits tobacco plant growth. Here we show that the inhibition of plant growth was caused by reduced cell expansion as well as by abnormal cell division and differentiation. We found that deletion of the C-terminally located catalytic domain of the protein abolished the ectopic effects of NtSET1 on plant growth. Our results indicate that histone H3 lysine 9 methylation is a critical mark of epigenetic control for plant development.


Acute insulin response to intravenous glucagon in polycystic ovary syndrome.
In order to evaluate the acute insulin response after i.v. injection of glucagon in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo-ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2 days later, a glucagon test (1 mg i.v.). Patients were analysed according to their degree of obesity; the insulin release after glucagon injection for lean PCOS subjects and control women was not statistically significantly different. Conversely obese PCOS patients had higher insulin secretion after both i.v. glucagon and OGTT when compared to the other groups. Moreover the insulin secretory patterns were heterogeneously represented in lean and obese PCOS women. When the patients were analysed according to their insulinaemic response to OGTT, normoinsulinaemic PCOS women and control subjects had a similar insulin response to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin response (P < 0.0001). Moreover, a highly significant relationship was found between the insulin response to OGTT and to glucagon administration in the PCOS population (P < 0.0001; r = 0.73), which was maintained also after controlling for obesity. Our results are consistent with the hypothesis that PCOS patients could have an insulin hyper-response to glucagon administration, that is partially independent from obesity and related to their insulinaemic status. Moreover, the glucagon test could represent an effective alternative to OGTT in screening insulin disorders of PCOS patients (at least in the absence of other risk factors), due to its reliability, simplicity, and speed of performance.


The volume-outcome effect for abdominal aortic surgery: differences in case-mix or complications?
Variation in postoperative complications after abdominal aortic surgery contributes to differences in mortality between high- and low-volume hospitals. Hospitals with high surgical volume have been shown to have lower operative mortality rates for complex vascular surgery than those with low volumes. Differences in the rates of complications among hospitals may explain this variation in mortality. Adult patients who underwent abdominal aortic surgery in Maryland from 1994 to 1996 (N = 2987) were included. The primary dependent variable was in-hospital mortality and the independent variables included hospital surgical volume, patient case-mix variables, and several specific postoperative complications. Two sequential analyses using multiple logistic regression were performed to determine the relative importance of independent variables in predicting mortality. Hospitals with high surgical volume had a lower mortality rate (5.6%) than those with medium (6.8%) and low (8.7%) volumes (P =.03). In the first multivariate analysis, after adjusting for patient case-mix, having surgery at a high-volume hospital remained associated with a 37% reduction in mortality (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.42-0.92; P =.02). Patients at high-volume hospitals had a decreased relative risk (RR) of several complications: pulmonary failure (RR, 0.45; 95% CI, 0.36-0.55), reintubation (RR, 0.53; 95% CI, 0.44-0.64), pneumonia (RR, 0.74; 95% CI, 0.55-0.99), cardiac complications (RR, 0.63; 95% CI, 0.51-0.78), and shock (RR 0.27; 95% CI, 0.10-0.75). In the second multivariate analysis, which included complications, hospital volume was no longer a significant predictor of mortality. However, several postoperative complications remained significant predictors of mortality. The effect of hospital volume on mortality after abdominal aortic surgery is attributable to differences in postoperative complications and not preoperative differences in case-mix. Efforts to reduce the rates of postoperative complications may reduce mortality rates at low-volume hospitals.


Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation.
We show that pentaerythritol tetranitrate reductase (PETNR), a member of the 'ene' reductase old yellow enzyme family, catalyses the asymmetric reduction of a variety of industrially relevant activated alpha,beta-unsaturated alkenes including enones, enals, maleimides and nitroalkenes. We have rationalised the broad substrate specificity and stereochemical outcome of these reductions by reference to molecular models of enzyme-substrate complexes based on the crystal complex of the PETNR with 2-cyclohexenone 4a. The optical purity of products is variable (49-99% ee), depending on the substrate type and nature of substituents. Generally, high enantioselectivity was observed for reaction products with stereogenic centres at Cbeta (>99% ee). However, for the substrates existing in two isomeric forms (e.g., citral 11a or nitroalkenes 18-19a), an enantiodivergent course of the reduction of E/Z-forms may lead to lower enantiopurities of the products. We also demonstrate that the poor optical purity obtained for products with stereogenic centres at Calpha is due to non-enzymatic racemisation. In reactions with ketoisophorone 3a we show that product racemisation is prevented through reaction optimisation, specifically by shortening reaction time and through control of solution pH. We suggest this as a general strategy for improved recovery of optically pure products with other biocatalytic conversions where there is potential for product racemisation.


Counting and classifying small objects by far-field light scattering.
An approach to small particle counting and classification is proposed in which the size and shape distribution is determined from the far-field pattern of light scattered by the particles. By presuming that the scattering function for each particle species is known from auxiliary experiments or calculations, a general result applicable to irregular particles as well as simply shaped particles is obtained. Inversion formulas, by which the particle distribution is determined from the far-field data, are presented in forms suitable for digital or optical processing. An experimental approach to the design of a real-time optical counting and classifying instrument is suggested.


Risks and benefits of anticoagulation in atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry.
Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC. We analyzed OAC use among 10,098 patients with AF from 174 community-based outpatient practices enrolled in 2010-2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS₂), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS₂ scores, from 53% for CHADS₂=0 to 80% for CHADS₂≥2 (P<0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 (P<0.001). A significant interaction existed between ATRIA and CHADS₂ scores (P=0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS₂ stroke risk had a smaller impact on use of OAC. In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.


Recovery from central nervous system changes following volatile substance misuse.
This review examines cognitive, neurological, and neuroanatomical recovery associated with abstinence from volatile substance misuse (VSM). Articles describing functional or structural brain changes longitudinally or cross-sectional reports comparing current and abstinent users were identified and reviewed. A significant lack of empirical studies investigating central nervous system recovery following VSM was noted. The few case reports and group studies identified indicated that cognitive and neurological impairments appear to follow a progression of decline and progression of recovery model, with the severity of impairment related to the duration and severity of misuse, blood lead levels among leaded petrol misusers, and the duration of abstinence for recovery. By contrast, severe neurological impairment known as lead encephalopathy from sniffing leaded petrol occurred as more catastrophic or abrupt damage to cerebellar processes that may never fully recover. Neuroanatomical damage may not recover even with prolonged abstinence.


Up-regulation of uncoupling proteins by beta-adrenergic stimulation in L6 myotubes.
Catecholamine-induced and beta-adrenergic receptor (beta-AR)-mediated thermogenesis in skeletal muscle is a significant component of whole-body energy expenditure. Skeletal muscle expresses uncoupling protein (UCP) 2 and UCP3, which can dissipate the transmitochondrial electrochemical gradient and thereby may be involved in regulation of energy metabolism. We investigated the effects of beta-AR stimulation on UCP2 and UCP3 expression in L6 myotubes. Stimulation of the cells with epinephrine increased the UCP3 mRNA level transiently at 6 h, and also the UCP2 mRNA level at 6-24 h. The stimulatory effects of epinephrine were also observed in the presence of carbacyclin and 9-cis retinoic acid, and mimicked by isoproterenol and salbutamol (beta2-AR agonists), but abolished by propranolol and ICI-118,551 (beta2-AR antagonists). Pharmacological and mRNA analyses revealed the existence of beta2-AR, but not beta1- and beta3-ARs, in L6 myotubes. These results suggested that catecholamines up-regulate UCP2 and UCP3 expression through direct action on the beta2-AR in skeletal muscle.


Identification of 'extinct' freshwater mussel species using DNA barcoding.
Freshwater mollusks are highly imperiled, with 70% of the North American species extinct, endangered, or at risk of extinction. Impoundments and other human impacts on the Coosa River of Alabama, Georgia and Tennessee of the southeastern USA alone are believed to have caused 50 mollusk species extinctions, but uncertainty over boundaries among several putatively closely related species makes this number preliminary. Our examination of freshwater mussels collected during an extensive survey of the upper-drainage basin, DNA barcoding and molecular phylogenetic analyses confirm the rediscovery of four morphospecies in the genus Pleurobema (Unionidae) previously thought to be extinct from the upper Coosa basin. A fifth 'extinct' form was found in an adjoining basin. Molecular data show that the Coosa morphologies represent at least three species-level taxa: Pleurobema decisum, P. hanleyianum and P. stabile. Endemism is higher than currently recognized, both at the species level and for multispecies clades. Prompt conservation efforts may preserve some of these taxa and their ecosystem.


Stability and structure of protonated clusters of ammonia and water, H+(NH3)m (H2O)n.
Mass spectrometric experiments show that protonated mixed ammonia/water clusters predominant exist in three forms namely H(+)(NH(3))(4)(H(2)O)(n), H(+)(NH(3))(5)(H(2)O)(n), and H(+)(NH(3))(6)(H(2)O)(n) (n = 1-25). For the first two series the collisional activation mass spectra are dominated by loss of water, whereas ions of the latter series preferably lose ammonia. The quantitative characteristics of these observations are reproduced by quantum chemical calculations that also provide insight into the geometrical structures of the clusters. Although the experiments and the calculations agree that clusters with five ammonia are thermodynamically preferred, this does not indicate a rigid tetrahedral structure with one central ammonium covered with an inner solvation shell of four ammonia molecules, with water outside. Instead, water and ammonia have comparable affinities to the binding sites of the first shell, with a preference for ammonia for the first two sites, and water for the last two. The "leftover" ammonia molecules bind equally strong as water molecules to sites in the second shell due to synergistic hydrogen binding. Finally, it is discussed whether the observation of enhanced stability of the H(+)(NH(3))(5)(H(2)O)(20) in terms of magic numbers and associated geometries may be related to a tetrahedral ammonium core encapsulated in a dodecahedral (H(2)O)(20) structure, typically found in clathrates.


Exploring Care Needs of Partners of Transgender and Gender Diverse Individuals in Co-Transition: A Qualitative Interview Study.
Scientific knowledge on the impact of a gender-affirming transition on intimate partners of transgender and gender diverse (TGD) individuals is limited. It is unclear which care needs partners have and which role health care professionals can play during this transition process. The aim of this study was to explore the unique experiences and care needs of people partnering with TGD people in the context of a gender-affirming transition. A qualitative research method was chosen, and a semi-structured interview was conducted with a sample of nine participants. After transcription, thematic analysis was used to analyse the data. Three main themes, with three subthemes each, were identified: (1) intrapersonal processes, with (1a) the process of acceptance, (1b) concerns surrounding the medical transition and (1c) impact on sexual orientation as subthemes; (2) dyadic processes, with (2a) the importance of mutual commitment, (2b) experiences regarding intimacy and (2c) relational growth as subthemes; and (3) perception of support, with (3a) need for support, (3b) the importance of support and (3c) evaluation of support as subthemes. The results suggest that health care providers can help partners to navigate the process of a gender-affirming transition; however, the care needs of partners are currently not satisfied with the available professional support.


One-and-a-half decades of HIV/AIDS in Tamil Nadu: how much do patients know now?
Tamil Nadu has experienced the impact of HIV/AIDS for one-and-a-half decades and is considered a trailblazer in India in terms of combating the infection. So what are the knowledge levels among 292 HIV patients at Government Hospital for Thoracic Medicine and Christian Medical College? Latent class analysis revealed that it was not adequate. Television and peer contact were found to be most effective as source of knowledge for HIV. Patients who were in contact with health personnel might be expected to have more information but they came out with low scores. Association of knowledge with socio-demographic characteristics revealed that education, occupation, income, place of residence, and age were important predictors. Future information, education and communication programmes need to consider the variation across different socio-demographic groups as a basis for targeting education programmes.


Italian evidence-based recommendations for the management of ankylosing spondylitis: the 3E Initiative in Rheumatology.
The 3E (Evidence, Expertise, Exchange) Initiative is a multinational effort of rheumatologists aimed at developing evidence-based recommendations addressing specific questions relevant to clinical practice. The objective of the Italian part of the 3E Initiative was to develop new recommendations designed to help Italian rheumatologists in everyday clinical practice management of patients suffering from ankylosing spondylitis (AS). An international scientific committee selected a set of questions concerning the diagnosis, monitoring, and treatment of AS using a Delphi procedure. Evidence-based answers to each question were sought by a systematic literature search in MedLine for papers published up to August 2006. A panel of 55 Italian rheumatologists with expertise in the field of AS used the evidence thus gathered to develop recommendations, filling gaps in evidence with their expert opinion. After discussion and votes, the panel developed 12 statements/recommendations: 3 concerning diagnosis (low back pain approach, early diagnosis, and GPs referral recommendations); 3 concerning monitoring (disease activity, severity, and prognosis), and 6 concerning treatment (bisphosphonates role; treatment of enthesitis; inter-agent safety/efficacy, long-term safety/efficacy, efficacy on different disease manifestations, and the role on inflammatory bowel disease flare precipitation of NSAIDs/COX-II inhibitors). Italian recommendations for the management of AS in everyday practice were developed. Their dissemination and implementation in daily clinical practice should help to improve practice uniformity and eventually optimize the management of AS patients.


Not Just an Accident: A Case of Insulinoma.
Insulinomas are a rare cause of recurrent hypoglycemia in non-diabetic patients. Diagnosis requires hypoglycemia (plasma glucose <50 mg/dL), neuroglycopenic symptoms, and prompt relief of symptoms following the administration of glucose, known as Whipple's triad. The gold standard diagnostic tests are measuring insulin, C-peptide, and glucose during a 72-hour fast. In the preoperative period and in patients with unresectable or metastatic tumors, medical management with diazoxide and octreotide can be considered for recurrent hypoglycemia. We present a case of insulinoma in a 37-year-old woman who initially presented after a seizure-related motor vehicle accident. Upon admission, her initial glucose level was 32 mg/dL, indicating a likely hypoglycemic seizure. During her hospitalization, she had recurrent episodes of fasting and postprandial hypoglycemia, ranging from 32-70 mg/dL. She exhibited the characteristics of Whipple's triad when values dropped below 50 mg/dL. These episodes necessitated continuous infusions of 10% dextrose. Tests for insulin autoantibodies, sulfonylurea screens, and thyroid function yielded unremarkable results. A 72-hour fasting test was initiated to investigate potential endogenous causes of excessive insulin production. Laboratory results from a venous glucose level of 46 mg/dL indicated a notable rise in C peptide and insulin levels, alongside beta hydroxybutyrate suppression, all of which fulfilled the diagnostic criteria for insulinoma. An abdominal magnetic resonance imaging (MRI) unveiled a 1.3 cm mass in the pancreatic tail. This case emphasizes the importance of employing a focused approach when evaluating non-diabetic individuals displaying hypoglycemia with positive Whipple's triad. This targeted method not only enables early detection of this rare condition but also assists in eliminating other common causes of recurrent hypoglycemia in non-diabetic individuals. Moreover, in addition to this diagnosis being rare, it is important to note that patients with insulinomas typically do not exhibit a glucose level low enough to induce seizures during their initial presentation.


International Center of Excellence for Malaria Research for South Asia and Broader Malaria Research in India.
The Malaria Evolution in South Asia (MESA) International Center of Excellence for Malaria Research (ICEMR) conducted research studies at multiple sites in India to record blood-slide positivity over time, but also to study broader aspects of the disease. From the Southwest of India (Goa) to the Northeast (Assam), the MESA-ICEMR invested in research equipment, operational capacity, and trained personnel to observe frequencies of Plasmodium falciparum and Plasmodium vivax infections, clinical presentations, treatment effectiveness, vector transmission, and reinfections. With Government of India partners, Indian and U.S. academics, and trained researchers on the ground, the MESA-ICEMR team contributes information on malaria in selected parts of India.


In situ mesh repair of parastomal hernias.
Options for the repair of parastomal hernias include contralateral transposition or in situ repair. The latter can be accomplished either primarily or with prosthetic mesh. Concerns with mesh include possible gut erosion and infection. Recurrence rates in the literature are dismal regardless of technique. We retrospectively reviewed our experience with this problem focusing on in situ repairs. We identified 9 patients who underwent 10 in situ repairs. Of these, 6 were women, average age was 69.4 years, and stomas had been constructed for cancer in 6, inflammatory bowel disease in 2, and incontinence in 1. Eight patients had colostomies; one had an ileostomy. All patients were symptomatic from their hernias. Repairs were performed an average of 8 years after stoma construction. Hernia repair was performed transabdominally in four and through a parastomal incision in six. Complications included hematoma formation requiring evacuation in one and delayed resumption of oral intake secondary to nausea and cramps in three. Of the 9 initial repairs, 1 recurred (11%) and was repaired without subsequent failure. No mesh erosions or wound infections have occurred. This technique is safe and may be preferable to contralateral placement of the stoma.


Gene network and canonical pathway analysis in prostate cancer: a microarray study.
The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 down-regulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1beta and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two up- and down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways. Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.


Factors Associated with Medication Adherence to Long-Acting Injectable Antipsychotics: Results from the STAR Network Depot Study.
Long-acting injectable (LAI) antipsychotics are prescribed to people with severe psychiatric disorders who show poor adherence to oral medication. The present paper examined factors potentially associated with medication adherence to LAI treatment. The STAR (Servizi Territoriali Associati per la Ricerca) Network Depot Study was a multicenter, observational, prospective study that enrolled 461 subjects initiating a LAI from 32 Italian centers. After 6 and 12 months of treatment, we evaluated differences between participants with high (≥5 points) and low (<5 points) medication adherence using Kemp's 7-point scale in sociodemographic, clinical, psychopathological, and drug-related variables. Factors that differed significantly between the two groups were entered for multivariate logistic regression. Six months after enrollment, participants with high medication adherence were younger, living with other people, had lower Brief Psychiatric Rating Scale (BPRS) total scores, lower adverse events, and a more positive attitude toward medication than participants with low adherence. Multivariate regression confirmed lower BPRS resistance and activation scores, absence of adverse events, and positive attitude toward medication as factors significantly associated with good adherence. After 12 months, all BPRS subscales were significantly lower in the high adherence group, which also showed a more positive attitude toward medication. BPRS resistance and attitude toward medication were confirmed as factors associated with medication adherence. Our findings suggest that adherence to LAI is principally related to attitude toward medication and traits of suspiciousness/hostility. Quality of patient-clinician relationship and tailored psychoeducational strategies may positively affect adherence in people undergoing psychopharmacological treatment, including LAI.


Real-Time Wireless Platform for In Vivo Monitoring of Bone Regeneration.
For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.